Curriculum Vitaes
Profile Information
- Affiliation
- Division of Analytical pathology, Oncology Innovation Center, Fujita Health University, Research Promotion Headquarters
- Degree
- 博士(医学)(名古屋市立大学)
- J-GLOBAL ID
- 201601018477634559
- researchmap Member ID
- 7000016197
Research History
8-
Apr, 2024 - Present
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Apr, 2021 - Mar, 2024
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Apr, 2017 - Mar, 2021
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Mar, 2016 - Mar, 2017
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Sep, 2014 - Feb, 2016
Education
2Major Committee Memberships
7-
Nov, 2024 - Present
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Apr, 2024 - Present
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2024 - Present
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2024 - Present
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2019 - Present
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2019 - Present
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Apr, 2022 - Mar, 2024
Awards
5-
Dec, 2024
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May, 2022
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2016
Major Papers
65-
Pathology international, Dec 11, 2024 Peer-reviewedLead authorCorresponding authorCD5 expression is seen in 5%-10% of de novo diffuse large B-cell lymphomas (DLBCLs). Primary large B-cell lymphoma of the central nervous system (PCNS-LBCL) also exhibits CD5 expression in a minority of cases, however, clinicopathological and molecular features remain largely unclarified. Here we present the clinical, molecular, and pathological features of 11 CD5-positive (+) PCNS-LBCL cases, occupying 6.7% of all 165 PCNS-LBCLs diagnosed in our institutions. While CD5+ systemic DLBCL has been recognized as a distinctive subgroup showing an aggressive clinical course, no obvious differences were found between CD5+ and CD5-negative subgroups among the present CNS patients clinically. MYD88 p.L265P and CD79B p.Y196 mutations were detected in eight (73%) and seven (64%) cases, respectively, supporting previous reports. Notably, the microenvironmental immune cells were universally PD-L1/CD274-positive, and the higher levels tended to present favorable overall survival, as already evidenced in the PCNS-LBCL series. In contrast, neoplastic PD-L1/CD274 expression was undetectable in all cases. Indeed, no structural variations or copy number alterations involving PD-1 ligands were detected by targeted-capture sequencing and fluorescence in situ hybridization. While further studies are warranted, we may have confirmed similarity between PCNS-LBCLs and intravascular large B-cell lymphomas from a molecular standpoint.
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Non-coding RNA Research, 9(1) 76-83, Mar, 2024 Peer-reviewedCorresponding author
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Neuropathology : official journal of the Japanese Society of Neuropathology, Nov 2, 2023 Peer-reviewedLead authorSubependymal giant cell astrocytoma (SEGA) is a low-grade periventricular tumor that is closely associated with tuberous sclerosis complex (TSC). SEGA typically arises during the first two decades of life and rarely arises after the age of 20-25 years. Nevertheless, it has also been reported that glioma histologically resembling SEGA, so-called SEGA-like astrocytoma, can arise in neurofibromatosis type 1 (NF1) patients, even in the elderly. Herein, we report a case of SEGA-like circumscribed astrocytoma arising in the lateral ventricle of a 75-year-old woman. Whole-exome sequencing revealed a somatic variant of NF1. Methylation array analysis led to a diagnosis of "methylation class glioblastoma, IDH-wildtype, mesenchymal-type (GBM, MES)" with a high calibrated score (0.99). EGFR amplification, CDKN2A/B homozygous deletion, chromosomal +7/-10 alterations, and TERT promoter mutation, typical molecular abnormalities usually found in GBM, were also observed. While most reported cases of SEGA-like astrocytoma have arisen in NF1 patients, the patient was neither TSC nor NF1. Near total removal was accomplished with endoscopic cylinder surgery. At the 36-month follow-up, there was no tumor recurrence without adjuvant therapies. This clinical behavior did not match GBM. SEGA-like astrocytoma of the elderly is rare, and this is the oldest case reported so far. In addition, high-grade molecular features found in circumscribed tumor remain unclear. Further investigations among larger series are needed for clarifying the underlying molecular mechanisms.
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Neuropathology, Sep 7, 2022 Peer-reviewedLead author
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Neuropathology : official journal of the Japanese Society of Neuropathology, 41(5) 335-348, Jul 13, 2021 Peer-reviewedLead authorCorresponding authorPrimary central nervous system lymphomas (PCNSLs) rarely exhibit intratumoral hemorrhage. The differential diagnosis of hemorrhagic neoplasms of the central nervous system (CNS) currently includes metastatic carcinomas, melanomas, choriocarcinomas, oligodendrogliomas, and glioblastomas. Here we present the clinical, radiological, pathological, and molecular genetic features of six cases of PCNSL associated with intratumoral hemorrhage. The median age of patients was 75 years, with male predominance. While conventional PCNSLs were associated with low cerebral blood volume (CBV), perfusion magnetic resonance imaging (MRI) revealed elevated CBV in three cases, consistent with vascular proliferation. All six cases were diagnosed pathologically as having diffuse large B-cell lymphoma (DLBCL) with a non-germinal center B-cell-like (non-GCB) phenotype; marked histiocytic infiltrates and abundant non-neoplastic T-cells were observed in most cases. Expression of vascular endothelial growth factor and CD105 in the lymphoma cells and the small vessels, respectively, suggested angiogenesis within the neoplasms. Neoplastic cells were immunohistochemically negative for programmed cell death ligand 1 (PD-L1), while immune cells in the microenvironment were positive for PD-L1. Mutations in the MYD88 gene (MYD88) (L265P) and the CD79B gene (CD79B) were detected in five and one case, respectively. As therapeutic modalities used for PCNSLs differ from those that target conventional hemorrhagic neoplasms, full tissue diagnoses of all hemorrhagic CNS tumors are clearly warranted.
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Brain tumor pathology, 37(3) 111-117, Jul, 2020 Peer-reviewedLead authorCorresponding authorThe CIC-DUX4 translocation is the most common genetic alteration of small round cell sarcomas without EWSR1 rearrangement. These "Ewing-like sarcomas" usually occur in peripheral soft tissues, and rare primary central nervous system (CNS) tumors have been described. We report a rare case of primary spinal intramedullary Ewing-like sarcoma harboring CIC-DUX4 translocation. A 23-year-old man presented with weakness in the extremities. Magnetic resonance imaging revealed a large intramedullary tumor spanning C3-C5 with heterogeneous enhancement following gadolinium administration. Histologically, most of the tumor displayed dense myeloid proliferation composed of medium- to slightly small-sized primitive cells. Postoperatively, he received local adjuvant radiation therapy without tumor progression for 10 months. Target RNA sequencing analysis revealed the CIC-DUX4 fusion gene. Methylation array analysis resulted in a diagnosis of "methylation class CNS Ewing sarcoma family tumor with CIC alteration". Although this tumor lacked characteristic histological features such as lobular structures in association with desmoplastic stroma, relatively uniform nuclei with prominent nucleoli and eosinophilic cytoplasm, which are often found in CIC-rearranged sarcomas of soft tissue, were identified. Recently, many CNS and soft tissue tumors require genetic analysis for precise diagnosis. To consider certain molecular testing, careful histological examination is essential.
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Pathology international, 69(6) 372-377, Jun, 2019 Peer-reviewedLead authorCorresponding authorGlioneuronal tumor (GNT) is a rare central nervous system neoplasm composed of glial and neuronal components. Making the specific diagnosis of GNT can be challenging due to histopathological and genetical similarities among some GNTs and low-grade gliomas. We report a case of GNT with rosette-forming glioneuronal tumor, dysembryoplastic neuroepithelial tumor, and pilocytic astrocytoma-like morphology harboring FGFR1 mutation. A 16-year-old female presented with absence seizures. Magnetic resonance imaging revealed a right temporal lobe mass with multinodular enhancement by gadolinium administration. The tumor was mostly composed of oligodendrocyte-like cells (OLCs) with variable perinuclear haloes. Abundant Rosenthal fibers and eosinophilic granular bodies were identified. Neither mitotic figures nor areas of necrosis were seen. Focal neurocytic rosette features, involving ring-like arrays of OLCs around eosinophilic cores, were observed. Direct sequencing showed a missense mutation in FGFR1 K656E, whereas FGFR1 N546K, PIK3CA, and BRAF V600E were intact. KIAA1549-BRAF fusion was not detected by fluorescence in situ hybridization analysis.
Misc.
27-
BRAIN PATHOLOGY, 29 174-175, Feb, 2019
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Neuro-oncology, 20(6) 810-817, May 18, 2018 Peer-reviewedBackground: Single-gene mutation syndromes account for some familial glioma (FG); however, they make up only a small fraction of glioma families. Gliomas can be classified into 3 major molecular subtypes based on isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion. We hypothesized that the prevalence of molecular subtypes might differ in familial versus sporadic gliomas and that tumors in the same family should have the same molecular subtype. Methods: Participants in the FG study (Gliogene) provided samples for germline DNA analysis. Formalin-fixed, paraffin-embedded tumors were obtained from a subset of FG cases, and DNA was extracted. We analyzed tissue from 75 families, including 10 families containing a second affected family member. Copy number variation data were obtained using a first-generation Affymetrix molecular inversion probe (MIP) array. Results: Samples from 62 of 75 (83%) FG cases could be classified into the 3 subtypes. The prevalence of the molecular subtypes was: 30 (48%) IDH-wildtype, 21 (34%) IDH-mutant non-codeleted, and 11 (19%) IDH-mutant and 1p/19q codeleted. This distribution of molecular subtypes was not statistically different from that of sporadic gliomas (P = 0.54). Of 10 paired FG samples, molecular subtypes were concordant for 7 (κ = 0.59): 3 IDH-mutant non-codeleted, 2 IDH-wildtype, and 2 IDH-mutant and 1p/19q codeleted gliomas. Conclusions: Our data suggest that within individual families, patients develop gliomas of the same molecular subtype. However, we did not observe differences in the prevalence of the molecular subtypes in FG compared with sporadic gliomas. These observations provide further insight into the distribution of molecular subtypes in FG.
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Brain pathology (Zurich, Switzerland), 28(2) 172-182, Mar, 2018 Peer-reviewed
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Neuropathology : official journal of the Japanese Society of Neuropathology, 37(4) 351-357, Aug, 2017 Peer-reviewed
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Neuropathology : official journal of the Japanese Society of Neuropathology, 37(4) 335-340, Aug, 2017 Peer-reviewedLead authorCorresponding author
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Neuropathology : official journal of the Japanese Society of Neuropathology, 36(5) 480-484, Oct, 2016 Peer-reviewedLead author
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Journal of neuropathology and experimental neurology, 75(2) 167-74, Feb, 2016 Peer-reviewed
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The American journal of surgical pathology, 40(2) 279-84, Feb, 2016 Peer-reviewedLead author
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JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 74(6) 607-607, Jun, 2015
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Human pathology, 45(6) 1192-8, Jun, 2014 Peer-reviewedLead author
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診断病理, 31(1) 19-24, 2014 Peer-reviewedLead authorCorresponding author
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Leukemia & lymphoma, 54(8) 1742-6, Aug, 2013 Peer-reviewed
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Human pathology, 43(8) 1322-7, Aug, 2012 Peer-reviewedLead author
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Pathology international, 62(2) 93-8, Feb, 2012 Peer-reviewed
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Internal medicine (Tokyo, Japan), 51(22) 3125-9, 2012 Peer-reviewed
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Human pathology, 42(9) 1297-304, Sep, 2011 Peer-reviewed
Major Books and Other Publications
11Major Professional Memberships
7Research Projects
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科学研究費助成事業, 日本学術振興会, Apr, 2025 - Mar, 2028
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科学研究費助成事業, 日本学術振興会, Apr, 2025 - Mar, 2028
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新潟大学脳研究所 新潟大学脳研究所共同利用・共同研究, Nov, 2024 - Mar, 2025
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Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Japan Society for the Promotion of Science, Apr, 2021 - Mar, 2024
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日東学術振興財団 研究助成, 2022 - 2023